1. Field of the Invention
This invention is directed to methods for synthesizing factor Xa inhibitors as well as to the synthesis of intermediates and pharmaceutically acceptable salts thereof. Also described herein are compositions comprising substantially pure betrixaban free base or betrixaban maleate salt.
2. State of the Art
Factor Xa, a serine protease, plays an important role in the blood coagulation pathway. Direct inhibition of factor Xa has been considered to be an efficient anticoagulant strategy in the treatment of thrombotic diseases.
U.S. Pat. No. 6,376,515 B2 discloses a class of benzamide based compounds as specific factor Xa inhibitors. In particular, U.S. Pat. No. 6,376,515 B2 describes a compound identified as Example 206, which is also disclosed in U.S. Pat. No. 6,835,739 B2 as Example 206 and herein identified as betrixaban, which has the chemical formula of Formula I:

In light of the relevance of the benzamide compounds in treating thrombotic diseases, there exists a need in an efficient method of making the compounds and their intermediates.